ReviewSignal transduction and targeted therapy2024
Protein neddylation and its role in health and diseases.
Review in Signal transduction and targeted therapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 103 papers.
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Who cites it
103 citing papers in PubMed, 116 citations in OpenAlex.
- Crosstalk between ubiquitination and other post-translational modifications in cardiovascular diseases.iScience · 2026Review
- E3 Ubiquitin Ligases in MASH-Associated Liver Fibrosis: Mechanisms and Therapeutic Opportunities.Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- ABTB1, as an E3 ubiquitin ligase, suppresses Th17 cell differentiation and mitigates autoimmune inflammation by promoting STAT3 ubiquitination and degradation.Cellular & molecular immunology · 2026Article
- Disease-specific tau polymorphs are associated with unique protein networks across proteinopathies.The EMBO journal · 2026Article
- Species-dependent activities of the PINK1-parkin axis.Translational neurodegeneration · 2026Review
- Endothelial deletion of the neddylation E2 enzyme UBE2M inhibits tumor growth by promoting nonproductive angiogenesis.The Journal of clinical investigation · 2026Article
- GPR56 and CD319 identify distinct cytotoxic-associated DP and DN T-cell subsets in early systemic lupus erythematosus.Clinical rheumatology · 2026Article
- Article
- Protein Post-Translational Modifications in UV-Induced Skin Damage.Experimental dermatology · 2026Review
- A guide to mapping ubiquitin and ubiquitin-like E3 ligases to their substrates.The FEBS journal · 2026Review
- PSMA6 drives non-small cell lung cancer progression by stabilizing NEDD8 and activating NF-κB signaling.Translational lung cancer research · 2026Article
- URMylation Signaling Pathway in Cancer: Molecular Mechanisms and Therapeutic Opportunities.Current issues in molecular biology · 2026Review
- Neddylation as a molecular integrator of metabolic dysfunction and endothelial dysfunction in type 2 diabetes.Acta pharmacologica Sinica · 2026Review
- Targeting cancer-intrinsic protein neddylation bypasses the loss of JAK/STAT signaling and overcomes acquired resistance to immunotherapy.Research square · 2026Article
- Protein neddylation as a therapeutic target: challenges and opportunities.The Journal of clinical investigation · 2026Review
- Neddylation: from regulatory mechanisms to clinical implications in cancer.Journal of advanced research · 2026Review
- Neddylation of NFATc1 and Runx2 regulates osteoclast-osteoblast balance and represents a dual-action therapeutic target for postmenopausal osteoporosis.Experimental & molecular medicine · 2026Article
- Overcoming Resistance in Triple-Negative Breast Cancer: A Translational Perspective on Next-Generation DNA Damage Response Inhibitors and Synthetic Lethality.Molecules (Basel, Switzerland) · 2026Review
- Targeting OTUD7A-HINT1 deubiquitination activates mTOR signaling for CNS regeneration.Cell death & disease · 2026Article
- Review
43 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 4 institutions in 1 country.
Funding
Abstract
NEDD8 (Neural precursor cell expressed developmentally downregulated protein 8) is an ubiquitin-like protein that is covalently attached to a lysine residue of a protein substrate through a process known as neddylation, catalyzed by the enzyme cascade, namely NEDD8 activating enzyme (E1), NEDD8 conjugating enzyme (E2), and NEDD8 ligase (E3). The substrates of neddylation are categorized into cullins and non-cullin proteins. Neddylation of cullins activates CRLs (cullin RING ligases), the largest family of E3 ligases, whereas neddylation of non-cullin substrates alters their stability and activity, as well as subcellular localization. Significantly, the neddylation pathway and/or many neddylation substrates are abnormally activated or over-expressed in various human diseases, such as metabolic disorders, liver dysfunction, neurodegenerative disorders, and cancers, among others. Thus, targeting neddylation becomes an attractive strategy for the treatment of these diseases. In this review, we first provide a general introduction on the neddylation cascade, its biochemical process and regulation, and the crystal structures of neddylation enzymes in complex with cullin substrates; then discuss how neddylation governs various key biological processes via the modification of cullins and non-cullin substrates. We further review the literature data on dysregulated neddylation in several human diseases, particularly cancer, followed by an outline of current efforts in the discovery of small molecule inhibitors of neddylation as a promising therapeutic approach. Finally, few perspectives were proposed for extensive future investigations.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.